2023 Fiscal Year Final Research Report
Causes of epigenomic abnormalities in Alzheimer's disease and their implications for neurodegeneration
| Project/Area Number |
21K07553
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 52030:Psychiatry-related
|
|---|
| Research Institution | Jikei University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
品川 俊一郎 東京慈恵会医科大学, 医学部, 准教授 (90459628)
|
|---|
| Project Period (FY) |
2021-04-01 – 2024-03-31
|
| Keywords | アルツハイマー病 / DNAメチル化 / 認知症 / 軽度認知障害 / エピジェネティクス / COASY / 単純ヘルペスウイルス1型 |
|---|
| Outline of Final Research Achievements |
In Alzheimer's disease (AD), changes in DNA methylation levels are thought to influence the accumulation of abnormal proteins and neurodegeneration. The applicants discovered that blood COASY DNA methylation levels change in AD patients. In this study, they identified 132 sites with differences in DNA methylation levels between AD patients and non-demented elderly individuals. Furthermore, they revealed that infection with herpes simplex virus type 1 (HSV-1) affects the DNA methylation of COASY. Specifically, the capsid protein VP26 was suggested to impact host DNA methylation changes by binding to the DNA methylation enzyme DNMT3A. These results are expected to lead to the development of new diagnostic methods and treatments for AD.
|
| Free Research Field |
精神医学
|
| Academic Significance and Societal Importance of the Research Achievements |
COASYはCoA合成酵素をコードし、神経変性疾患とも関連があるにも関わらず、基礎研究は少なく、詳細な機能は未解明である。また、COASYはがんとの関連も知られるが、がん細胞でCOASYをノックダウンしても細胞の増殖性に影響はなく、CoA濃度を保つ未知のメカニズムがあると報告される。そのため、COASYが関わる代謝異常を明らかにすることは学術的にも有意義で、他分野への波及効果も大きい。
また、本研究で、COASYやその他のDNAメチル化の意義が明らかとなれば、それ自体でADの発症を予測するバイオマーカーとなる。これはADの予防にも活かすことが可能となる。
|
